POS0207 UNRAVELING THE COMPLEX INTERACTION BETWEEN DISEASE ACTIVITY AND FATIGUE IN EARLY RA: A MEDIATION ANALYSIS WITH DATA FROM THE CareRA TRIAL
Authors: M. Doumen, S. Pazmino, D. Bertrand, D. De Cock, J. Joly, R. Westhovens, P. Verschueren
Journal: Annals of the Rheumatic Diseases (2022)

Background Fatigue is recognized as one of the most important symptoms of rheumatoid arthritis (RA). Although inflammation is often proposed as the predominant pathophysiological mechanism, many patients with RA continue to experience fatigue despite inflammatory disease control. The relationship between RA disease activity and fatigue appears to be complex and is likely confounded by cognitive, emotional and social aspects. Objectives To unravel the complex interaction between disease activity and fatigue in early RA. Methods Data were analyzed from the 2-year treat-to-target trial Care in early RA (CareRA), which compared different remission-induction DMARD regimens, either with or without bridging glucocorticoids, in treatment-naïve patients with early RA. Fatigue was measured on a visual analog scale (VAS) at every study visit. The association between inflammatory disease activity (DAS28-CRP) and fatigue (VAS) over time was studied with a multilevel mediation analysis, including as mediators the individual components of the DAS28-CRP, pain (VAS), disability (HAQ), psychosocial aspects (Short-Form 36 [SF-36]), illness perceptions (Revised Illness Perception Questionnaire [IPQ-R]), and sleep quality (Pittsburgh Sleep Quality Index [PSQI]). Results A total of 356 patients were included in these analyses, with a mean (SD) fatigue (VAS) of 48/100 (24) at study initiation. Although there was a consistently positive association between DAS28-CRP and fatigue over time, this association was fully mediated by patient global assessment (PGA) and pain, and to a lesser extent by SF-36 Mental Health and the PSQI global score (Figure 1). Full mediation implies the absence of a significant direct association between DAS28-CRP and fatigue after adjusting for these mediators. In addition, no mediating effect was found for tender/swollen joint counts or CRP. Figure 1. Mediation analysis of the association between DAS28-CRP and fatigue (VAS) over time. Reported are the standardized regression coefficients with indicators of significance (* p &lt; 0.05; ** p &lt; 0.01; *** p &lt; 0.001). DAS28-CRP = Disease Activity Score in 28 joints with C-reactive protein, SJC28/TJC28 = swollen/tender joint count in 28 joints, HAQ = Health Assessment Questionnaire, SF-36 = Short-Form 36, MH = mental health, RE = emotional role functioning, SF = social functioning, IPQ-R = Revised Illness Perception Questionnaire, PSQI = Pittsburgh Sleep Quality Index Conclusion Our mediation analysis suggests that the relationship between disease activity and fatigue in early RA is complex and fully mediated by aspects of wellbeing like pain, mental health, sleep quality, and the patient’s overall assessment of disease. These results imply a mainly indirect relation between fatigue and inflammation. Clinicians should reserve specific attention for the psychosocial determinants of fatigue, particularly when no improvement is seen with DMARDs. Disclosure of Interests Michaël Doumen: None declared, Sofia Pazmino: None declared, Delphine Bertrand: None declared, Diederik De Cock: None declared, Johan Joly: None declared, Rene Westhovens Speakers bureau: Honoraria for lectures: - Celltrion - Gilead - Galapagos, Consultant of: - Celltrion - Gilead - Galapagos, Patrick Verschueren Speakers bureau: MSD Galapagos Eli Lilly, Consultant of: Sanofi Galapagos Pfizer Gilead, Grant/research support from: Pfizer Chair Management of Early Rheumatoid Arthritis at KU Leuven Belgium